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Chronic inflammation - Coggle Diagram
Chronic inflammation
Innate immune cells
Recruitment of macrophages dominates compared to neutrophil abundace in acute inflammation
- elimination failure + continuous macro recruitment
-> short lived neutrophils die off
-> macorophages > within 48 hours
Monocytes migrate into extravascular tissue early in acute reaction
- differentiate into larger macrophages - epithelioid cells
- longer 1/2 life, greater phagocytotic activity
Macrophages filter:
- particulate matter, microbes, dead/dying cells
Act as sentinel cell to alert other immune cells
- material may remain in vesicle for long time
Lymphocytes maintain presence of phagocytes
- T and B cells mobilise at stimulus site via adhesion and chemokine directed movement
Lymphocyte/macrophage interaction
- Macrophage display antigen to MHC class I and II
- Activate using costimulatory molecules and IL-2
- Macrophage recruitment via lymphocyte released factors; MIF traps macrophages
-
Active B cells = plasma cells
- Produce antibodies against persistent antigens or damaged tissue
- accumulate at sites of chronic inflmmmation; aggregate to form germinal centre in 2' lymphoid organs
Granuloma
- aggregration of macrophages forming in response to chronic inflammation
Main purposes
- Barrier to dissemination
- Local environment for immune cell killing
- Prevent inflammation
- Granuloma in Tb
- macrophages fail to kill bacteria and lyse
- recruit more macrophages
- Lymphocyte recruitment due to cytokine release from macrophages
- e.g. Mtb antigen presentation(Mo) and IFN-gamma(Tcell)
- Macrophage fusion to form syncytia
- large mass of multinucleated cells
- driven by IL-4 secretion and myocbacterial substances
- greater nutrient access without leaving mass
- Repair and fibroblast stimulation via M2
- fibrosis walls off infection; prevent spread
- slow growth of Mtb(24hr doubling time) prevents overwhelming response
- Bacterial lipids disable macrophages
- cant pump xs LDL
- foam cells = cholesterol rich source of bacteria food
- Macrophage death
- caesum forms at necrotic centre
- Mtb can't multiply: low pH/anaerobic environment
- CAN persist within tubercles
Antigen role
Acute inflammation
- antigen detected; cleared by neutrophils and macrophages
- adaptive immune cells recruited
- antigen cleared or host dies from infection/inflammation
Chronic inflammation
- antigen persists; stimulation of immune system for long time
- removal of antigen e.g. face masks or antibiotics
CC: Silicosis >20 yearssilicone particles deposited in alveoli of lungs
- non organic material so can't be phagocytosed
- continual buildup - persistent inflammatory stimulus
CC: TuberculosisInfection by acid-fast rods Mycobacterium tuberculosis via aerosol transmission
- infection begins at lung via invasion of macrophages
- mycolic acid create thick protective hydrophobic cel wall
- entry avoids oxidative burst; Mtb recruits C2a fragment or activates alt pathway
- fluorescent labelling indicates phagosome able to recruit GTPase Rab5/not Rab7 - Mtb prevents lysosome fusion - unhindered intracelular proliferation
- efficient stress response; reduce ROS damage
- type VII SS escapes phagosome?
Conclusion: macrophages can't eliminate - pathogen persistence
Repair mechanism
IDEAL: dead cells and inflammatory exudate cleared completely
ANTIGEN PERSISTENCE: necrotic foci conversion into fibrous tissue
Macrophage evolution over timeActivation with IL-4 and IL-13
- released from Tcells, mast cells, eosinophils
Create M2 macrophages
- anti inflammatory and promote tissue repair
M2 release anti inflammatory cytokines
- IL-10 and TGF beta
- stimulate fibroblast proliferation
- form highly vascularised granulation tissue
Granulation tissue
- major role: occupy site of lost tissue
- scaffold for collagen lay down
Mature scar tissue is:
- hypovascular
- cellularly poor
- mainly type I collagen
- collagenous mass that contracts; permitting optimal tissue function
- vascularisation and collagen deposition may become excessive
Autoimmune diseases
CC: Rheumatoid arthiritisInitial external trigger e.g. infection, injury, smoking
- autoimmune reaction characterised by SYNOVIAL hypertrophy and chronic JOINT inflammation
- inflammation sustained through epitope spreading
- inflammation and proliferation of SYNOVIUM forming PANNUS; destroys normal joint structure
Treatment
- NSAIDs: relieve pain, reduce minor inflammation --> can't reduce LTE of RA
- corticosteroids - inhibit PLA2; useful short term
- DMARDs e.g. methotrexate reduce significantly; reduce and prevent joint dmg; weeks/months to take effect